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세미나 담당교수 : 2021-2학기 강찬희(chanhee.kang@snu.ac.kr), 정충원(cwjeong@snu.ac.kr), 천종식(jchun@snu.ac.kr)
조 교 : 홍석영(880-4418, young.hong023@snu.ac.kr)
호암교수회관 : 5572, 교수회관: 5241, 두레미담: 9358, 라쿠치나: 1631.

[초청강연] The Lysosome in Nutrient Sensing and Cellular Growth Control

2021-12-06l 조회수 269

일시: 2021-12-10 11:00 ~ 13:00
발표자: Robert Zoncu (UC Berkeley Dept. of Molecular & Cell Biology)
담당교수: 생명과학부
장소: https://snu-ac-kr.zoom.us/j/84309485441
In order to grow, cells must tightly coordinate biosynthetic processes with catabolic programs. The
master regulator, mechanistic target of rapamycin complex 1 (mTORC1) kinase, integrates signals
from nutrients, hormones and energy to control the balance between cellular growth and repair
programs. In a key step, nutrients drive the localization of mTORC1 to the lysosomal membrane,
where mTORC1 becomes competent to phosphorylate its downstream targets. Cholesterol was
recently identified as a major nutrient input for lysosomal mTORC1 activation. Cholesterol sensing
occurs upstream of the heterodimeric Rag GTPases, and involves its active exchange between the
limiting membranes of lysosomes and the endoplasmic reticulum. Moreover, this process is negatively
regulated by the cholesterol exporter, Niemann-Pick C1 (NPC1) protein, loss of which leads to
mTORC1 hyperactivation and to mTORC1-dependent disruption of autophagy and mitochondrial
function, implicating dysregulated mTORC1 signaling as a pathogenic driver of Niemann-Pick type C.
Despite these advances, our understanding of how cholesterol regulates mTORC1 remains
fragmentary. In particular, we lack a complete knowledge of the cholesterol-regulated proteins that
translate lysosomal cholesterol levels to modulation of the Rag GTPases. I will present our recent
effort to unravel lysosomal cholesterol sensing through a combination of organelle proteomics,
bioinformatic analysis and functional assays both in vitro and in cell. This work illuminates the
fundamental logic of lysosomal nutrient sensing, and could increase the understanding of Niemann-
Pick type C pathogenesis.